Faims apparatus and method using carrier gases that contain a trace amount of a dopant species

ABSTRACT

Disclosed is a method and apparatus for improving at least one of a peak separation and a signal intensity relating to an ion of interest being transmitted through an analyzer region of a FAIMS apparatus. A method according to the instant invention includes a step of introducing ions including an ion of interest into an analyzer region of a FAIMS. A flow of a doped carrier gas other than air is also provided through the analyzer region. The doped carrier gas includes a carrier gas and a trace amount of a predetermined dopant gas, the predetermined dopant gas selected for improving at least one of a peak separation and a signal intensity relating to the ion of interest relative to the peak separation and the signal intensity relating to the ion of interest in the presence of the carrier gas only. The ion of interest is selectively transmitted through the analyzer region in the presence of the doped carrier gas, and detected at a detector.

FIELD OF THE INVENTION

The instant invention relates generally to high field asymmetricwaveform ion mobility spectrometry (FAIMS), more particularly theinstant invention relates to an apparatus and method for selectivelytransmitting ions according to the FAIMS principle using carrier gasesthat contain a trace amount of a dopant species.

BACKGROUND OF THE INVENTION

High sensitivity and amenability to miniaturization for field-portableapplications have helped to make ion mobility spectrometry (IMS) animportant technique for the detection of many compounds, includingnarcotics, explosives, and chemical warfare agents as described, forexample, by G. Eiceman and Z. Karpas in their book entitled “IonMobility Spectrometry” (CRC, Boca Raton, 1994). In IMS, gas-phase ionmobilities are determined using a drift tube with a constant electricfield. Ions are separated in the drift tube on the basis of differencesin their drift velocities. At low electric field strength, for example200 V/cm, the drift velocity of an ion is proportional to the appliedelectric field strength and the mobility, K, which is determined fromexperimentation, is independent of the applied electric field.Additionally, in IMS the ions travel through a bath gas that is atsufficiently high pressure that the ions rapidly reach constant velocitywhen driven by the force of an electric field that is constant both intime and location. This is to be clearly distinguished from thosetechniques, most of which are related to mass spectrometry, in which thegas pressure is sufficiently low that, if under the influence of aconstant electric field, the ions continue to accelerate.

E. A. Mason and E. W. McDaniel in their book entitled “TransportProperties of Ions in Gases” (Wiley, New York, 1988) teach that at highelectric field strength, for instance fields stronger than approximately5,000 V/cm, the ion drift velocity is no longer directly proportional tothe applied electric field, and K is better represented by K_(H), anon-constant high field mobility term. The dependence of K_(H) on theapplied electric field has been the basis for the development of highfield asymmetric waveform ion mobility spectrometry (FAIMS). Ions areseparated in FAIMS on the basis of a difference in the mobility of anion at high field strength, K_(H), relative to the mobility of the ionat low field strength, K. In other words, the ions are separated due tothe compound dependent behavior of K_(H) as a function of the appliedelectric field strength.

In general, a device for separating ions according to the FAIMSprinciple has an analyzer region that is defined by a space betweenfirst and second spaced-apart electrodes. The first electrode ismaintained at a selected dc voltage, often at ground potential, whilethe second electrode has an asymmetric waveform V(t) applied to it. Theasymmetric waveform V(t) is composed of a repeating pattern including ahigh voltage component, V_(H), lasting for a short period of time t_(H)and a lower voltage component, V_(L), of opposite polarity, lasting alonger period of time t_(L). The waveform is synthesized such that theintegrated voltage-time product, and thus the field-time product,applied to the second electrode during each complete cycle of thewaveform is zero, for instance V_(H)t_(H)+V_(L)t_(L)=0; for example+2000 V for 10 μs followed by −1000 V for 20 μs. The peak voltage duringthe shorter, high voltage portion of the waveform is called the“dispersion voltage” or DV, which is identically referred to as theapplied asymmetric waveform voltage.

Generally, the ions that are to be separated are entrained in a streamof gas flowing through the FAIMS analyzer region, for example between apair of horizontally oriented, spaced-apart electrodes. Accordingly, thenet motion of an ion within the analyzer region is the sum of ahorizontal x-axis component due to the stream of gas and a transversey-axis component due to the applied electric field. During the highvoltage portion of the waveform an ion moves with a y-axis velocitycomponent given by v_(H)=K_(H)E_(H), where E_(H) is the applied field,and K_(H) is the high field ion mobility under operating electric field,pressure and temperature conditions. The distance traveled by the ionduring the high voltage portion of the waveform is given byd_(H)=v_(H)t_(H)=K_(H)E_(H)t_(H), where t_(H) is the time period of theapplied high voltage. During the longer duration, opposite polarity, lowvoltage portion of the asymmetric waveform, the y-axis velocitycomponent of the ion is v_(L)=KE_(L), where K is the low field ionmobility under operating pressure and temperature conditions. Thedistance traveled is d_(L)=v_(L)t_(L)=KE_(L)t_(L). Since the asymmetricwaveform ensures that (V_(H) t_(H))+(V_(L) t_(L))=0, the field-timeproducts E_(H)t_(H) and E_(L)t_(L) are equal in magnitude. Thus, ifK_(H) and K are identical, d_(H) and d_(L) are equal, and the ion isreturned to its original position along the y-axis during thenegative-cycle of the waveform. If at E_(H) the mobility K_(H)>K, theion experiences a net displacement from its original position relativeto the y-axis. For example, if a positive ion travels farther during thepositive portion of the waveform, for instance d_(H)>d_(L), then the ionmigrates away from the second electrode and eventually will beneutralized at the first electrode.

In order to reverse the transverse drift of the positive ion in theabove example, a constant negative dc voltage is applied to the secondelectrode. The difference between the dc voltage that is applied to thefirst electrode and the dc voltage that is applied to the secondelectrode is called the “compensation voltage” (CV). The CV voltageprevents the ion from migrating toward either the second or the firstelectrode. If ions derived from two compounds respond differently to theapplied high strength electric fields, the ratio of K_(H) to K may bedifferent for each compound. Consequently, the magnitude of the CV thatis necessary to prevent the drift of the ion toward either electrode isalso different for each compound. Thus, when a mixture including severalspecies of ions, each with a unique K_(H)/K ratio, is being analyzed byFAIMS, only one species of ion is selectively transmitted to a detectorfor a given combination of CV and DV. In one type of FAIMS experiment,the applied CV is scanned with time, for instance the CV is slowlyramped or optionally the CV is stepped from one voltage to a nextvoltage, and a resulting intensity of transmitted ions is measured. Inthis way a CV spectrum showing the total ion current as a function ofCV, is obtained.

U.S. Pat. No. 5,420,424, issued to Carnahan and Tarassov on May 30,1995, teaches a FAIMS device having cylindrical electrode geometry andelectrometric ion detection, the contents of which are incorporatedherein by reference. The FAIMS analyzer region is defined by an annularspace between inner and outer cylindrical electrodes. In use, ions thatare to be separated are entrained into a flow of a carrier gas and arecarried into the analyzer region via an ion inlet orifice. Once insidethe analyzer region, the ions become distributed all the way around theinner electrode as a result of the carrier gas flow and ion-ionrepulsive forces. The ions are selectively transmitted within theanalyzer region to an ion extraction region at an end of the analyzerregion opposite the ion inlet end. In particular, a plurality of ionoutlet orifices is provided around the circumference of the outerelectrode for extracting the selectively transmitted ions from the ionextraction region for electrometric detection. Of course, theelectrometric detectors provide a signal that is indicative of the totalion current arriving at the detector. Accordingly, the CV spectrum thatis obtained using the Carnahan device does not include informationrelating to an identity of the selectively transmitted ions. It is alimitation of the Carnahan device that the peaks in the CV spectrum arehighly susceptible to being assigned incorrectly.

Replacing the electrometric detector with a mass spectrometer detectionsystem provides an opportunity to obtain additional experimental datarelating to the identity of ions giving rise to the peaks in a CVspectrum. For instance, the mass-to-charge (m/z) ratio of ions that areselectively transmitted through the FAIMS at a particular combination ofCV and DV can be measured. Additionally, replacing the mass spectrometerwith a tandem mass spectrometer makes it possible to perform afull-fledged structural investigation of the selectively transmittedions. Unfortunately, the selectively transmitted ions are difficult toextract from the analyzer region of the Carnahan device for subsequentdetection by a mass spectrometer. In particular, the orifice plate of amass spectrometer typically includes a single small sampling orifice forreceiving ions for introduction into the mass spectrometer. Thisrestriction is due to the fact that a mass spectrometer operates at amuch lower pressure than the FAIMS analyzer. In general, the size of thesampling orifice into the mass spectrometer is limited by the pumpingefficiency of the mass spectrometer vacuum system. In principle, it ispossible to align the sampling orifice of a mass spectrometer with asingle opening in the FAIMS outer electrode of the Carnahan device;however, such a combination suffers from very low ion transmissionefficiency and therefore poor detection limits. In particular, theCarnahan device does not allow the selectively transmitted ions to beconcentrated for extraction through the single opening. Accordingly,only a small fraction of the selectively transmitted ions are extractedfrom the analyzer region, the vast majority of the selectivelytransmitted ions being neutralized eventually upon impact with anelectrode surface.

Guevremont et al. describe the use of curved electrode bodies, forinstance inner and outer cylindrical electrodes, for producing atwo-dimensional atmospheric pressure ion focusing effect that results inhigher ion transmission efficiencies than can be obtained using, forexample, a FAIMS device having parallel plate electrodes. In particular,with the application of an appropriate combination of DV and CV an ionof interest is focused into a band-like region between the cylindricalelectrodes as a result of the electric fields which change with radialdistance. Focusing the ions of interest has the effect of reducing thenumber of ions of interest that are lost as a result of the ionsuffering a collision with one of the inner and outer electrodes.

In WO 00/08455, the contents of which are incorporated herein byreference, Guevremont and Purves describe an improved tandem FAIMS/MSdevice, including a domed-FAIMS analyzer. In particular, the domed-FAIMSanalyzer includes a cylindrical inner electrode having a curved surfaceterminus proximate the ion outlet orifice of the FAIMS analyzer region.The curved surface terminus is substantially continuous with thecylindrical shape of the inner electrode and is aligned co-axially withthe ion outlet orifice. During use, the application of an asymmetricwaveform to the inner electrode results in the normal ion-focusingbehavior as described above, except that the ion-focusing action extendsaround the generally spherically shaped terminus of the inner electrode.This causes the selectively transmitted ions to be directed generallyradially inwardly within the region that is proximate the terminus ofthe inner electrode. Several contradictory forces are acting on the ionsin this region near the terminus of the inner electrode. The force ofthe carrier gas flow tends to influence the ion cloud to travel towardsthe ion-outlet orifice, which advantageously also prevents the ions frommigrating in a reverse direction, back towards the ionization source.Additionally, the ions that get too close to the inner electrode arepushed back away from the inner electrode, and those near the outerelectrode migrate back towards the inner electrode, due to the focusingaction of the applied electric fields. When all forces acting upon theions are balanced, the ions are effectively captured in every direction,either by forces of the flowing gas, or by the focusing effect of theelectric fields of the FAIMS mechanism. This is an example of athree-dimensional atmospheric pressure ion trap, as described in greaterdetail by Guevremont and Purves in WO 00/08457, the contents of whichare incorporated herein by reference.

Guevremont and Purves further disclose a near-trapping mode of operationfor the above-mentioned tandem FAIMS/MS device, which achieves iontransmission from the domed-FAIMS to a mass spectrometer with highefficiency. Under near-trapping conditions, the ions that accumulate inthe three-dimensional region of space near the spherical terminus of theinner electrode are caused to leak from this region, being pulled by aflow of gas towards the ion-outlet orifice. The ions that leak out fromthis region do so as a narrow, approximately collimated beam, which ispulled by the gas flow through the ion-outlet orifice and into a smallerorifice leading into the vacuum system of the mass spectrometer.Accordingly, such tandem FAIMS/MS devices are highly sensitiveinstruments that are capable of detecting and identifying ions ofinterest at part-per-billion levels.

The prior art FAIMS devices typically use a carrier gas comprising apurified flow of one of nitrogen, oxygen and air. For instance, Carnahanand Tarassov in U.S. Pat. No. 5,420,424 teach the use of dehumidifiedair as the carrier gas. In WO 00/08455, Guevremont and Purves teachproviding a compressed gas, such as for instance one of air andnitrogen, which is passed through a charcoal/molecular sieve gaspurification cylinder before being introduced into the analyzer regionof a FAIMS device.

In Rev. Sci. Instrum., Vol. 69, No. 12, December 1998, the contents ofwhich are herein incorporated by reference, Purves et al. report resultsthat were obtained through experimentation and which illustrate thedeleterious effects of having concomitant compounds in the carrier gasstream. In particular, Purves et al. reported that the CV spectraobtained when the FAIMS device was operated at elevated temperature aredramatically different than corresponding CV spectra obtained prior toelevating the temperature. It was hypothesized that water molecules andother contaminants were being desorbed from the various internalsurfaces of the FAIMS device as the temperature was raised. Subsequentinteractions between the ions of interest, in these experiments positiveions, and the desorbed species resulted in significant suppression ofthe detector signal when the FAIMS device was operated in a mode inwhich the polarity of the dispersion voltage is positive (P 1). Purveset al. state that the P1 mode is very sensitive to gas phase impurities.Conversely, a dramatic increase of the detector signal of the positiveions was observed under similar operating conditions when the FAIMSdevice was operated in a mode in which the polarity of the dispersionvoltage is negative (P2). Purves et al. suggest that several of theimpurities are observed in the P2 CV spectrum, which is in keeping withan initial increase in the total ion intensity as the various internalsurfaces are heated and the contaminant species are desorbed therefrom.Purves et al. do not suggest that the presence of a small amount ofwater or another contaminant in the carrier gas stream could be used toimprove the results that are obtained using FAIMS. Rather, they indicatethat their preliminary results suggest that the high sensitivity ofFAIMS to concomitant compounds in the gas stream and high sensitivity tochanges in analyte concentration will introduce difficulty inidentification of ions by FAIMS. This view is reiterated by the sameauthors in Rev. Sci. Instrum. Vol. 70, No. 2, February 1999, thecontents of which are herein incorporated by reference.

In WO 01/69646, the contents of which are herein incorporated byreference, Guevremont et al. describe in detail the effect of using gasmixtures to change the separation capabilities and signal intensity ofions transmitted through a FAIMS device._It was found that the behaviorof ions in these gas mixtures is not predictable based upon the behaviorof the ions in the individual gases in the mixture. This unexpectedbehavior led to unforeseen advantages for the analyses of several ionsusing a FAIMS device. However, the amount of each gas that was used toinduce a change was always in excess of one percent. Furthermore, manytypes of ions do not display such advantageous behavior in the types ofgas mixtures that were described in WO 01/69646.

It would be advantageous to provide a method and an apparatus forseparating ions according to the FAIMS principle that overcomes thelimitations of the prior art.

SUMMARY OF THE INVENTION

In accordance with an aspect of the invention there is provided anapparatus for selectively transmitting ions comprising: a high fieldasymmetric waveform ion mobility spectrometer comprising two electrodesdefining an analyzer region therebetween, the two electrodes disposed ina spaced apart arrangement for allowing ions to propagate therebetweenand for providing an electric field within the analyzer region resultingfrom the application of an asymmetric waveform voltage to at least oneof the two electrodes and from the application of a compensation voltageto at least one of the two electrodes, for selectively transmitting anion of interest at a given combination of asymmetric waveform voltageand compensation voltage; and, a doping portion for receiving a flow ofa carrier gas from a gas source and for controllably mixing a dopant gaswith the flow of a carrier gas to produce a doped carrier gas streamcontaining a predetermined concentration of the dopant gas, the dopingportion also in fluid communication with the analyzer region forproviding the doped carrier gas stream thereto, wherein during use thedoped carrier gas stream that is provided to the analyzer regioncontains less than 1% dopant gas by volume.

In accordance with another aspect of the invention there is provided anapparatus for selectively transmitting ions comprising: a high fieldasymmetric waveform ion mobility spectrometer comprising two electrodesdefining an analyzer region therebetween, the two electrodes disposed ina spaced apart arrangement for allowing ions to propagate therebetweenand for providing an electric field within the analyzer region resultingfrom the application of an asymmetric waveform voltage to at least oneof the two electrodes and from the application of a compensation voltageto at least one of the two electrodes, for selectively transmitting anion of interest at a given combination of asymmetric waveform voltageand compensation voltage; a carrier gas source for providing a flow of acarrier gas; a first containing portion for containing a first gasmixture including a first concentration of a dopant gas; a secondcontaining portion for containing a second gas mixture including asecond concentration of the dopant gas; and, a doping portion in fluidcommunication with the carrier gas source, the first containing portion,the second containing portion and the analyzer region, for receiving theflow of a carrier gas from the gas source and for controllably mixing atleast one of the first gas mixture and the second gas mixture with theflow of the carrier gas, to form a doped carrier gas stream containing apredetermined concentration of the dopant gas, and for providing thedoped carrier gas stream to the analyzer region, wherein during use thedoped carrier gas stream that is provided to the analyzer regioncontains less than 1% dopant gas by volume.

In accordance with another aspect of the invention there is provided amethod of selectively transmitting ions, comprising the steps of:introducing ions including an ion of interest into an analyzer region ofa high field asymmetric waveform ion mobility spectrometer; providing aflow of a doped carrier gas other than air through the analyzer region,the doped carrier gas including a carrier gas and a trace amount of apredetermined dopant gas, the predetermined dopant gas selected forimproving at least one of a peak separation and a signal intensityrelating to the ion of interest relative to the peak separation and thesignal intensity relating to the ion of interest in the presence of thecarrier gas only; and, selectively transmitting the ion of interestthrough the analyzer region in the presence of the doped carrier gas.

In accordance with another aspect of the invention there is provided amethod of selectively transmitting ions, comprising the steps of:providing an analyzer region defined by a space between two spaced-apartelectrodes; providing an electric field within the analyzer regionresulting from the application of an asymmetric waveform voltage to atleast one of the two electrodes and from the application of adirect-current compensation voltage to at least one of the twoelectrodes; providing a flow of a carrier gas from a carrier gas source;removing water vapour from the flow of a carrier gas to provide a flowof a dried carrier gas; adding a trace amount of a predetermined dopantgas to the flow of a dried carrier gas to provide a flow of a dopedcarrier gas; introducing the flow of a doped carrier gas into theanalyzer region; introducing ions including an ion of interest into theanalyzer region; and selectively transmitting the ion of interestthrough the analyzer region in the presence of the doped carrier gas.

In accordance with another aspect of the invention there is provided amethod of selectively transmitting ions, comprising the steps of:providing an analyzer region defined by a space between two spaced-apartelectrodes; providing an electric field within the analyzer regionresulting from the application of an asymmetric waveform voltage to atleast one of the two electrodes and from the application of adirect-current compensation voltage to at least one of the twoelectrodes; determining a suitable dopant gas for improving one of apeak separation and a signal intensity relating to an ion of interest;providing a flow of a carrier gas other than air through the analyzerregion, the carrier gas including a first gas and a trace amount of thesuitable dopant gas; introducing ions including the ion of interest intothe analyzer region; and, selectively transmitting the ion of interestthrough the analyzer region.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the invention will now be described inconjunction with the following drawings, in which similar referencenumbers designate similar items:

FIG. 1 is a simplified block diagram of a FAIMS apparatus according tothe prior art;

FIG. 2 is a simplified block diagram of a FAIMS apparatus according to afirst embodiment of the instant invention;

FIG. 3 is a simplified block diagram of a FAIMS apparatus according to asecond embodiment of the instant invention;

FIG. 4 a shows a schematic block diagram of the gas supply and gasmixing portions of the apparatus described with reference to FIG. 2,providing a 3:1 purified carrier gas to doped carrier gas ratio;

FIG. 4 b shows a schematic block diagram of the gas supply and gasmixing portions of the apparatus described with reference to FIG. 2,providing a 9:1 purified carrier gas to doped carrier gas ratio;

FIG. 4 c shows a schematic block diagram of the gas supply and gasmixing portions of the apparatus described with reference to FIG. 2,providing a 39:1 purified carrier gas to doped carrier gas ratio;

FIG. 4 d shows a schematic block diagram of the gas supply and gasmixing portions of the apparatus described with reference to FIG. 2,providing a 99:1 purified carrier gas to doped carrier gas ratio;

FIG. 5 is an alternative arrangement of the gas supply and gas mixingportions that is suitable for providing a desired amount of a dopant gasin a carrier gas stream of a FAIMS analyzer;

FIG. 6 a is a second alternative arrangement of the gas supply and gasmixing portions that is suitable for providing a desired amount of adopant gas in a carrier gas stream of a FAIMS analyzer, in a first modeof operation;

FIG. 6 b shows the arrangement of FIG. 6 a in a second mode ofoperation;

FIG. 7 shows a simplified block diagram of a domed-FAIMS analyzer foruse with the apparatus of either one of FIG. 2 and FIG. 3;

FIG. 8 a shows a CV spectrum for the +5 charge state of bovine insulinwhen a purified carrier gas stream is used;

FIG. 8 b shows a CV spectrum for the +5 charge state of bovine insulinwhen 250 ppm of 2-chlorobutane is added to the carrier gas stream;

FIG. 8 c shows a CV spectrum for the +5 charge state of bovine insulinwhen 500 ppm of 2-chlorobutane is added to the carrier gas stream;

FIG. 8 d shows a CV spectrum for the +5 charge state of bovine insulinwhen 750 ppm of 2-chlorobutane is added to the carrier gas stream;

FIG. 8 e shows a CV spectrum for the +5 charge state of bovine insulinwhen 1000 ppm of 2-chlorobutane is added to the carrier gas stream;

FIG. 9 a shows a CV spectrum for the +6 charge state of bovine insulinwhen a purified carrier gas stream is used;

FIG. 9 b shows a CV spectrum for the +6 charge state of bovine insulinwhen 250 ppm of 2-chlorobutane is added to the carrier gas stream;

FIG. 9 c shows a CV spectrum for the +6 charge state of bovine insulinwhen 500 ppm of 2-chlorobutane is added to the carrier gas stream;

FIG. 9 d shows a CV spectrum for the +6 charge state of bovine insulinwhen 750 ppm of 2-chlorobutane is added to the carrier gas stream;

FIG. 9 e shows a CV spectrum for the +6 charge state of bovine insulinwhen 1000 ppm of 2-chlorobutane is added to the carrier gas stream;

FIG. 10 a shows a CV spectrum for protonated methamphetamine obtainedusing a dehumidified carrier gas;

FIG. 10 b shows a CV spectrum for protonated methamphetamine obtainedusing a carrier gas containing a trace amount of water vapour;

FIG. 11 a shows a CV spectrum for protonated3,4-methylenedioxymethamphetamine obtained using a dehumidified carriergas;

FIG. 11 b shows a CV spectrum for protonated3,4-methylenedioxymethamphetamine obtained using a carrier gascontaining a trace amount of water vapour;

FIG. 12 a shows a CV spectrum for protonated3,4-methylenedioxyamphetamine obtained using a dehumidified carrier gas;

FIG. 12 b shows a CV spectrum for protonated3,4-methylenedioxyamphetamine obtained using a carrier gas containing atrace amount of water vapour;

FIG. 13 a shows a CV spectrum for protonated amphetamine obtained usinga dehumidified carrier gas;

FIG. 13 b shows a CV spectrum for protonated amphetamine obtained usinga carrier gas containing a trace amount of water vapour;

FIG. 14 is a simplified flow diagram for a method according to theinstant invention of selectively transmitting ions within a FAIMSanalyzer region using a carrier gas including a trace amount of an addedcomponent;

FIG. 15 is a simplified flow diagram for another method according to theinstant invention of selectively transmitting ions within a FAIMSanalyzer region using a carrier gas including a trace amount of an addedcomponent; and,

FIG. 16 is a simplified flow diagram for yet another method according tothe instant invention of selectively transmitting ions within a FAIMSanalyzer region using a carrier gas including a trace amount of an addedcomponent.

DETAILED DESCRIPTION OF THE DRAWINGS

The following description is presented to enable a person skilled in theart to make and use the invention, and is provided in the context of aparticular application and its requirements. Various modifications tothe disclosed embodiments will be readily apparent to those skilled inthe art, and the general principles defined herein may be applied toother embodiments and applications without departing from the spirit andthe scope of the invention. Thus, the present invention is not intendedto be limited to the embodiments disclosed, but is to be accorded thewidest scope consistent with the principles and features disclosedherein.

Referring to FIG. 1, shown is a FAIMS apparatus according to the priorart. The apparatus, shown generally at 10, includes an analyzer portion12, a control portion 14 and a gas source portion 16. The gas sourceportion 16 is in fluid communication with the analyzer portion via a gastransfer line 18. A flow controller or valve 20 is disposed at a pointalong the length of the gas transfer line 18 for adjusting a flow rateof a gas from the gas source portion 16. The analyzer portion 12includes a high field asymmetric waveform ion mobility spectrometer(FAIMS) 22. For instance, the FAIMS 22 is in the form of one of acylindrical geometry domed-FAIMS, a side-to-side FAIMS and a parallelplate FAIMS. An ionization source 24 is provided in communication withthe FAIMS 22 for providing sample ions thereto. During use, the ions ofinterest are transmitted through the FAIMS 22 and detected. Forinstance, the ions of interest are extracted from the FAIMS 22 forintroduction into a mass spectrometer 26. The mass spectrometer 26provides an electrical signal, which is proportional to a measured ioncurrent of the transmitted ions, to the control portion 14 via a firstcommunication line 34. For instance, the control portion 14 is amicro-computer including a processor 28 and a memory 30. The controlportion 14 is in electrical communication with a display device 32, forproviding information to a user of the apparatus 10. The control portion14 is also in electrical communication with the FAIMS 22 via a secondcommunication line 36 for controlling the application of an asymmetricwaveform voltage and a direct current compensation voltage to notillustrated electrodes of the FAIMS 22.

Referring still to FIG. 1, the apparatus 10 further includes a gasfilter, for instance a charcoal/molecular sieve filter 40, which isdisposed at a point along the gas transfer line 18 intermediate the gassource portion 16 and the analyzer portion 12. The purpose of the gasfilter is to remove traces of water and/or other contaminants from thegas that is provided from the gas source portion 16. As discussed supra,the prior art teaches that the presence of concomitant compounds in thegas stream leads to a decrease in at least one of the separationcapability, reproducibility, and the sensitivity of FAIMS. Accordingly,the prior art FAIMS devices are operated under carefully controlledconditions whereby such contaminants are absent within the FAIMSanalyzer region.

Referring now to FIG. 2, shown is a FAIMS apparatus according to a firstembodiment of the instant invention. The apparatus, shown generally at50, includes an analyzer portion 52, a control portion 54, a first gassource portion 56, a second gas source portion 64 and a gas-mixingportion 66. The first gas source portion 56 is in fluid communicationwith the analyzer portion via a gas transfer line 58. A first flowcontroller or valve 60 is disposed at a point along the length of thegas transfer line 58 for adjusting a flow rate of a first gas from thefirst gas source portion 56. A second flow controller or valve 62 isdisposed at a point along the length of a second gas transfer line 68that is intermediate the second gas source portion 64 and the mixingportion 66. The second flow controller or valve 62 is for adjusting aflow rate of a second gas from a second gas source portion 64. Theanalyzer portion 52 includes a high field asymmetric waveform ionmobility spectrometer (FAIMS) 70. For instance, the FAIMS 70 is in theform of one of a cylindrical geometry domed-FAIMS, a side-to-side FAIMSand a parallel plate FAIMS. An ionization source 72 is provided incommunication with the FAIMS 70 for providing sample ions thereto.During use, the ions of interest are transmitted through the FAIMS 70and detected. For instance, the ions of interest are extracted from theFAIMS 70 for introduction into a mass spectrometer 74. The massspectrometer 74 provides an electrical signal, which is proportional toa measured ion current of the transmitted ions, to the control portion54 via a first communication line 76. For instance, the control portion54 is a micro-computer including a processor 78 and a memory 80. Thecontrol portion 54 is in electrical communication with a display device82, for providing information to a user of the apparatus 50. The controlportion 54 is also in electrical communication with the FAIMS 70 via asecond communication line 84 for controlling the application of anasymmetric waveform voltage and a direct current compensation voltage tonot illustrated electrodes of the FAIMS 70.

Referring still to FIG. 2, the apparatus 50 further includes a gasfilter, for instance a charcoal/molecular sieve filter 86, which isdisposed at a point along the gas transfer line 58 intermediate thefirst gas source portion 56 and the mixing chamber 66. The purpose ofthe gas filter is to remove traces of water and/or other contaminantsfrom the first gas provided from the first gas source portion 56. Thisis particularly important when a gas that is being used as a dopant gasis also present in unknown trace amounts in the first gas. For instance,the trace amounts of water and/or other contaminants originating fromthe first gas source portion 56 may be large relative to a desired finalconcentration of the dopant gas in the final carrier gas stream.Optionally, a not illustrated second gas filter is disposed at a pointalong the second gas transfer line 68 for removing traces of waterand/or other contaminants from the second gas provided from the secondgas source portion 64. Of course, the second gas filter must not removethe dopant gas contained within the second gas.

During use, the first gas is mixed with and dilutes the second gaswithin the gas-mixing portion 66. Preferably, the first gas comprises apurified carrier gas such as for instance one of purified oxygen,purified nitrogen and purified air. The second gas preferably comprisesa same purified carrier gas mixed with a known amount of a dopant gas.Alternatively, the second gas comprises a different purified carrier gasmixed with a known amount of a dopant gas. Preferably, the dopant gas ispresent in the second gas in an amount that is less than approximatelytwo percent by volume. Most preferably, the dopant gas is present in thesecond gas in an amount that is less than approximately 5000 ppm. Inparticular, the dopant gas is provided in the second gas in an amountthat, when diluted by the first gas, produces a final dopant gasconcentration of less than approximately one percent by volume.

The dopant gas is selected based upon a type of ion that is to beseparated. Since the effect of a particular dopant gas on a given typeof ion is difficult to predict, the selection of said dopant gasgenerally involves experimentation that is well within the ability ofone of skill in the art. Preferably, a plurality of dopant gases isidentified as being likely suitable for use with the given type of ions,prior to performing the experimental evaluation of the effectiveness ofeach one of the plurality of likely suitable dopant gases. For example,such identification may be performed by taking into account previousobservations relating to similar types of ions. Ultimately, trial anderror type experiments may be performed in order to identify theparticular dopant gas that yields improved results for the given type ofion. Similarly, experimentation is required to determine an optimalamount of the dopant gas within the carrier gas stream for improving atleast one of the sensitivity and ion separation capabilities of theFAIMS toward the given type of ion. Of course, the steps for selectingthe dopant gas and for determining the optimal amount of the dopant gaswithin the carrier gas stream need to be performed once only.Preferably, a library including a plurality of predetermined methods isavailable, each method including an identity and an optimal amount of adopant gas for analyzing a particular type of ion.

Referring now to FIG. 3, shown is a FAIMS apparatus according to asecond embodiment of the instant invention. Elements labeled with thesame numerals have the same function as those illustrated in FIG. 2. Theapparatus, shown generally at 90 does not include a gas filter at apoint along the gas transfer line 58. Accordingly, the first gas ispreferably absent traces of water and/or other contaminants thatadversely affect the sensitivity and/or separation capability of theFAIMS 50 toward the given type of ion.

Referring now to FIG. 4 a, shown is a schematic block diagram of the gassupply and gas mixing portions of the apparatus 50 described withreference to FIG. 2. Elements labeled with the same numerals have thesame function as those illustrated in FIG. 2. In the instant example,the first gas includes 0 ppm of the dopant gas, and the second gasincludes 1000 ppm of the dopant gas. In order to provide a carrier gasflow to the FAIMS 70 that includes, for instance, 250 ppm of the dopantgas, the ratio of a flow rate of the first gas through the first flowcontroller 60 to a flow rate of the second gas through the second flowcontroller 62 is set to 3:1, as indicated by the numerals that arebounded by the flow controllers 60 and 62, respectively. Referring nowto FIGS. 4 b, 4 c and 4 d, the ratios of flow rates that are required toachieve a dopant gas concentration of 100 ppm, 25 ppm and 10 ppm in thecarrier gas flow are 9:1, 39:1 and 99:1, respectively. Accordingly, highquality flow controllers are required to provide an accurately knownamount of the dopant gas in the carrier gas stream over a wide range ofdopant gas concentration values, such as for example 10 ppm to 1000 ppm.Alternatively, when dopant gas concentrations approaching the lowerlimit of the range are desired, the second gas source portion isreplaced with a source of a second gas containing a lower concentrationof the dopant gas, such that smaller ratios of flow rates are used toachieve the desired dopant gas concentration.

Referring now to FIG. 5, shown is an alternative arrangement of the gassupply and gas mixing portions that is suitable for providing a desiredfinal concentration of the dopant gas in the carrier gas stream of aFAIMS analyzer. According to the alternative arrangement, a purifiedcarrier gas absent the dopant gas is provided at first gas source 100and a second gas containing for example 1000 ppm of the dopant gas isprovided at second gas source 102. A first flow controller 106 isprovided for controllably varying a flow rate of the purified carriergas from the first gas source 100 to a mixing chamber 110, and a secondflow controller 108 is provided for controllably varying a flow rate ofthe second gas from the second gas source 102 to the mixing chamber 110.The purified carrier gas and the second gas are mixed within the mixingchamber 110, to produce a gas mixture including a trace amount of thedopant gas. Furthermore, a third flow controller 114 is provided forcontrollably varying a flow rate of the gas mixture from the mixingchamber 110 to a second mixing chamber 118. A fourth flow controller 116is provided for controllably varying a flow rate of a purified carriergas from a third gas source 112 to the second mixing chamber 118, whereit is mixed with the mixed gas to produce a carrier gas having a finaldopant gas concentration. The carrier gas having a final dopant gasconcentration is provided from the second mixing chamber 118 to theFAIMS.

In the example that is shown in FIG. 5, the mixing ratio of purifiedcarrier gas to the second gas is 9:1, resulting in a 10-fold dilution ofthe second gas. Purified carrier gas from the third gas source 112 isused to achieve a second 10-fold dilution of the mixed carrier gas to afinal concentration of 10 ppm. Step-wise dilution of a doped gas isadvantageous for several reasons. First, the second gas may be preparedwith an initial dopant gas concentration that is relatively large, suchas for example 1000 ppm. Accordingly, a wide range of final dopant gasconcentrations is accessible by varying the flow rates of purifiedcarrier gas and of the second gas, and by varying the number ofdilutions that is performed. For instance, omitting the second dilutionstep results in a final carrier gas concentration of 100 ppm instead of10 ppm. Secondly, performing two or more dilutions in series allowssmaller mixing ratios to be used during each dilution step, resulting insmaller errors associated with flow rate control. Advantageously, thereproducibility of the final dopant gas concentration is improved, andthe comparison of experimental data to calibration data obtained at aknown dopant gas concentration is more accurate. Optionally, thepurified carrier gases from the first and third gas sources 100 and 112,respectively, are different purified carrier gases.

Referring now to FIGS. 6 a and 6 b, shown is a second alternativearrangement of the gas supply and gas mixing portions that is suitablefor providing a desired amount of the dopant gas in the carrier gasstream of a FAIMS analyzer. According to the second alternativearrangement, two separate sources of doped carrier gas are provided. Inparticular, a first doped carrier gas source 122 containing a relativelyhigh concentration of dopant gas and a second doped carrier gas source130 containing a relatively low concentration of dopant gas are providedin fluid communication with a mixing chamber 128. For example, the firstdoped carrier gas source 122 contains 1000 ppm of the dopant gas and thesecond doped carrier gas source 130 contains 250 ppm of the dopant gas.A source of purified carrier gas 120 is also provided in fluidcommunication with the mixing chamber 128. Referring now to FIG. 6 a, afinal dopant gas concentration of 100 ppm is obtained by providing tothe mixing chamber 128 a flow of the purified carrier gas through afirst flow controller 124 that is nine times larger than a flow of thefirst doped carrier gas through a second flow controller 126. Referringnow to FIG. 6 b, the same final dopant gas concentration of 100 ppm isobtained by providing a 6:4 ratio of the purified carrier gas and thesecond doped carrier gas to the mixing chamber 128. Accordingly, theflow rates through the first flow controller 124 and a second flowcontroller 132 are similar, which reduces errors that are associatedwith operating one flow controller at a significantly lower flow ratecompared to a second flow controller. The alternative arrangement of thegas supply and gas mixing portions described with reference to FIGS. 6 aand 6 b support a wide range of final dopant gas concentrations.Optionally, the second doped carrier gas source 130 is replaced with anot illustrated second source of a purified carrier gas, for dilutingthe gas mixture produced within the mixing chamber 128.

Further optionally, the first and second doped carrier gas sources 122and 130, respectively, are in fluid communication with a not illustratedgas manifold, which is for receiving a flow of at least one of the firstand second doped carrier gases. The not illustrated gas manifold is alsoin fluid communication with the mixing chamber 128 for providing thereceived flow of at least one of the first and second doped carriergases thereto. The gas manifold functions as a flow selector forselectively switching between a flow of the first doped carrier gas anda flow of the second doped carrier gas. Optionally, the gas manifold canalso function as a flow combiner for providing a combined flow of gasincluding the first doped carrier gas and the second doped carrier gas,to the mixing chamber 128.

Referring now to FIG. 7, shown is a specific and non-limiting example ofan analyzer portion 52 that is suitable for use with the apparatus 50and 90 that are described with reference to FIGS. 2 and 3, respectively.In particular, the FAIMS 70 is provided in the form of a cylindricaldomed-FAIMS. FIG. 7 also shows an ionization source 72 and a detectionsystem 74 in the form of an electrospray ionization source and a massspectrometric detector, respectively. It should be clearly understood,however, that any one of a plurality of other FAIMS electrode geometriesmight be provided in place of the cylindrical domed-FAIMS electrodegeometry that is described with reference to FIG. 7. For instance, oneof a parallel plate geometry and a side-to-side geometry FAIMS isprovided as the FAIMS 70. Similarly, at least one of the electrosprayionization source and the mass spectrometric detector might be replacedby another suitable ionization source and another suitable detectionsystem, respectively.

Referring still to FIG. 7, the domed-FAIMS includes inner and outercylindrical electrodes 140 and 142, respectively, supported by anelectrically insulating material 144 in an overlapping, spaced-apartarrangement. The generally annular space between the inner electrode 140and the outer electrode 142 defines a FAIMS analyzer region 146. Thewidth of the analyzer region is approximately uniform around thecircumference of the inner electrode 140, and extends around a curvedsurface terminus 148 of the inner electrode 140. Inner electrode 140 isprovided with an electrical contact 158 through the insulating material144 for connection to a power supply 160 of the FAIMS 70, that duringuse is capable of applying a high voltage asymmetric waveform voltage(DV) and a low voltage dc compensation voltage (CV) to the inner FAIMSelectrode 140. A particular type of ion is transmitted through theanalyzer region 146 at a given combination of CV and DV, on the basis ofthe high field mobility properties of the ion.

An ion inlet orifice 150 is provided through the outer electrode 142 forintroducing ions produced at the ionization source 72 into the analyzerregion 146. For example, the ionization source 72 is in the form of anelectrospray ionization ion source including a liquid delivery capillary170, a fine-tipped electrospray needle 172 that is held at high voltage(power supply not shown) and a curtain plate 156 serving as acounter-electrode for electrospray needle 172. The liquid deliverycapillary 170 is in fluid communication with sample reservoir 174containing a solution of an ion precursor. Ions are produced by the verystrong electric field at the electrospray needle 172 from the solutionof an ion precursor. The potential gradient accelerates the ions awayfrom the electrospray needle 172, towards the curtain plate electrode156. A portion of the ions pass through an orifice 154 in the curtainplate electrode 156, become entrained in a flow of a carrier gas, whichis represented in FIG. 7 by a series of closed-headed arrows, and arecarried into the FAIMS analyzer region 146. The flow of a carrier gas isprovided through the analyzer region 146 to carry the ions toward an ionoutlet orifice 152 located opposite the curved surface terminus 148 ofthe inner electrode 140. The orifice 154 within the curtain plateelectrode 156 allows for the flow of a portion of the carrier gas in adirection that is counter-current to the direction in which the ions aretraveling near the ion inlet 150, so as to desolvate the ions beforethey are introduced into the analyzer region 146. Once inside the FAIMSanalyzer region 146, the ions are transmitted through an electric fieldthat is formed within the FAIMS analyzer region 146 by the applicationof the DV and the CV to the inner FAIMS electrode 140 via the electricalcontact 158. Since the electric field also extends around the curvedsurface terminus 148, the transmitted ions tend to be directed generallyradially inwardly towards the ion outlet orifice 152.

Referring still to FIG. 7, a mass spectrometer detector 74 is disposedexternal to the FAIMS analyzer region 146, and includes an orifice plate162 having an inlet orifice 164 extending therethrough. As will beapparent to one of skill in the art, the size of the inlet orifice 164is typically very small, being limited by the pumping efficiency of anot illustrated mass spectrometer vacuum system. The inlet orifice 164in the orifice plate 162 is aligned with the ion outlet orifice 152 ofthe domed-FAIMS apparatus such that ions being extracted through the ionoutlet orifice 152 enter the mass spectrometer inlet orifice 164. Thoseions that pass through the orifice 164 in the orifice plate 162 travelto a skimmer cone 166 within the differentially pumped region of themass spectrometer, and are analyzed within a mass analyzer 168 on thebasis of their mass-to-charge ratio. The mass spectrometer includes anot illustrated detector, such as for instance an electron multiplier,for providing an electrical signal that is proportional to a detectedion current.

Particular features of the invention will now be illustrated withreference to two specific and non-limiting examples. In the firstexample, trace amounts of 2-chlorobutane in a carrier gas stream areused to improve the separation capability of the +5 charge state ofbovine insulin and the +6 charge state of bovine insulin. An apparatussimilar to the one that is shown at FIG. 2 was used to obtaincompensation voltage spectra (CV spectra) for the +5 and +6 chargestates of bovine insulin. The analyzer portion of the apparatus includedthe elements that were described with reference to FIG. 7. In addition,a charcoal/molecular sieve filter was disposed at a point along thesecond gas transfer line 68 for removing traces of water and othercontaminants from the second gas before mixing with a purified carriergas. In the second example, trace amounts of water vapour in a carriergas stream are used to improve the signal intensity of amphetamine and aseries of related compounds.

EXAMPLE 1

Bovine insulin, having a molecular weight of 5735 Da, was obtained inpowdered form. A stock solution containing bovine insulin was preparedby dissolving a known amount of the bovine insulin powder in a solventcontaining 1% ACS grade glacial acetic acid (acetic acid) indistilled/deionized water (DDW). Running solutions containing bovineinsulin were prepared by adding known amounts of the stock solution,DDW, HPLC grade methanol (methanol), and acetic acid so that theconcentration of the bovine insulin was approximately 2 μM and thesolvent included a mixture of approximately 49.5% by volume DDW, 49.5%by volume methanol, and 1% by volume acetic acid. For example, toprepare 2 mL of a running solution, the following solutions weretransferred to a glass vial using eppendorf pipets: 990 μL of methanol,970 μL of DDW, 20 μL of a 200 μM stock solution, and 20 μL of aceticacid. The glass vial was sealed with a screw top cap and shaken toensure homogeneity of the solution.

A 250 μL syringe was rinsed at least three times with a solution blank,such as for example a solution without bovine insulin present andincluding approximately 1% by volume acetic acid in a mixture of 1:1DDW/methanol by volume. The 250 μL syringe was rinsed at least threetimes with the running solution before filling the 250 μL syringe withthe running solution for analysis. The 250 μL syringe served as thesample reservoir 174 of FIG. 7, which was in fluid communication withthe electrospray needle 172 via the liquid delivery capillary 170 fortransferring the running solution from the 250 μL syringe to theelectrospray needle 172. The electrospray needle 172 was prepared usinga new piece of fused silica capillary of approximately 50 cm in lengthand having a 50 μm inner diameter and a 180 μm outer diameter, which wasfit into a 10-cm long stainless steel capillary having a 200 μm innerdiameter and 430 μm outer diameter, and allowed to protrude about 1 mmbeyond the end of the stainless steel. This stainless steel capillary,in turn, protruded about 5 mm beyond the end of a larger stainless steelcapillary of 15 cm in length with a 500 μm inner diameter and a 1.6 mmouter diameter, that was used for structural support and application ofthe high voltage necessary for electrospray. A Harvard® Apparatus Model22 syringe pump (not shown) was used to deliver the solution from the250 μL syringe to the end of the fused silica capillary at a flow rateof 1 μL/min. Prior to analyzing the running solution, the ionizationsource 72 was flushed with a solution blank at a flow rate of 1 μL/minfor 10 minutes.

The tip of the electrospray needle 172 was placed approximately 1 cmaway from, and slightly off-centre at an angle of approximately 45degrees to, the curtain plate electrode 156 of the electrosprayionization source 72 of FIG. 7. Such an orientation of the electrosprayneedle 172 avoids the transfer of large droplets into the FAIMS analyzerregion 146. The electrospray needle 172 was held at approximately 4000 Vgenerating a current of about 180 nA for the running solution. Tooptimize the electrospray process, the distance that the fused silicacapillary protruded from the 10 cm long stainless steel capillary wasadjusted until the current was stable at a value near 180 nA. Thevoltage applied to the curtain plate electrode 156 was 1000 V and thecurtain plate electrode 156 was isolated from the FAIMS outer electrode142. The outer electrode 142 made electrical contact with the orificeplate 162 of the mass spectrometer, which were both held at +20 V. TheFAIMS 70 was operated in P2 mode; that is to say the asymmetric waveformhas a negative DV value. The width of the FAIMS analyzer region 146 wasapproximately 1.5 mm, and the width of an extraction region intermediatethe curved surface terminus 148 of the inner electrode 140 and the ionoutlet orifice 152 was approximately 1.7 mm.

To generate the asymmetric waveform for the analyses described herein, atuned electronic circuit was used that provided an appropriatecombination of a sinusoidal wave and its harmonic. These waveforms aremathematically described by the equation,V _(α)(t)=C+fD sin(ωt)+(1−f)D sin(2ωt−φ  (1)where V_(α)(t) represents the voltage of the waveform relative to thevoltage applied to the outer electrode 142 at a given time, t, C is thecompensation voltage, CV, which is changed stepwise from 4.36 to −17.24V during the acquisition of the spectra as is described below, D is themaximum voltage of the waveform or the dispersion voltage, DV=−3800 V, fis approximately 0.65, ω is the frequency (750 kHz), and φ is 90°.

Referring again to FIG. 2, industrial grade nitrogen gas was passedthrough the charcoal/molecular sieve filter 86 and a gas mixturecontaining 1000 ppm 2-chlorobutane in nitrogen was passed through aseparate molecular sieve filter (not shown) before the gases were mixedtogether in the mixing chamber 66 and introduced into the FAIMS 70.Referring again to FIG. 7, the flow rates of each of these gases wereadjustable and the total flow rate into a gas inlet 176 of the FAIMS 70was fixed at 1.2 L/min. Thus to obtain, for example, a mixturecontaining 250 ppm 2-chlorobutane in nitrogen as the doped carrier gas,the flow rate for the industrial grade nitrogen gas was set to 0.9 L/minand the flow rate for the gas mixture containing 1000 ppm 2-chlorobutanein nitrogen was set to 0.3 L/min. With the exception of 0 L/min, theflow rate of the gas mixture of 1000 ppm 2-chlorobutane in nitrogen wasvaried from 0.03 to 1.20 L/min giving a range of approximately 25 to1000 ppm of 2-chlorobutane in the nitrogen carrier gas. As is shown inFIG. 7, the total gas flow splits into two portions including a firstportion flowing out through the curtain plate orifice 154 in a directionthat is countercurrent to the arriving electrospray ions, therebyfacilitating desolvation of the electrospray ions. A second portion ofthe total gas flow carries the ions inward through the ion inlet orifice150 in the outer FAIMS electrode 142 and along the analyzer region 146of the device. Ions transmitted by the FAIMS device were detected usingthe API 300 triple quadrupole mass spectrometer.

Electrospray ionization of bovine insulin produces a distribution ofions of the form [M+zH]^(z+), where M is the molecular weight of bovineinsulin protein (5735 Da), z is a number (e.g., 5,6,7), and H is aproton attached to the bovine insulin protein. The value of z in thisexample can also be used to refer to the charge state of the ion. Foranalyzing electrospray generated ions from the running solutioncontaining bovine insulin, the mass spectrometer was set to monitor theintensity of detected ions of the m/z value of a particular charge stateso as to produce an CV spectrum. For example, when analyzing a runningsolution, the CV was scanned from 4.36 to −17.24 V in 240 incrementalsteps each of approximately −0.09 V. In one CV scan, charge state (z)+5was monitored, which means that an m/z value of 1148.0 was monitored.When the CV scan was initiated, the CV value was 4.36 V and thequadrupole mass analyzer was set to selectively detect m/z 1148.0 for1000 ms. The CV was then stepped to 4.27 V and the quadrupole massanalyzer selectively measured the ion intensity for another 1000 ms.This process of stepping the CV and selectively detecting m/z 1148.0 wasrepeated until a total of 241 points were obtained. From this data, aplot of the ion intensity as a function of the CV was obtained for the+5 charge state. Several of these plots were acquired with differentamounts of 2-chlorobutane added to the carrier gas. CV spectra for othercharge states were monitored in an analogous way using the same runningsolution.

FIGS. 8 a to 8 e show five CV spectra for the +5 charge state of bovineinsulin using a carrier gas comprising nitrogen mixed with differentamounts, for instance 0, 250, 500, 750, and 1000 ppm, respectively, of2-chlorobutane vapour. The ordinate in each plot represents the signalintensity of the +5 ion measured in counts per second, and the abscissarepresents the CV range between +4 to −17 V. FIG. 8 a shows an CVspectrum that was recorded with no 2-chlorobutane vapour present in thepurified carrier gas. FIG. 8 b shows a spectrum collected in a manneridentical to that in FIG. 8 a, but with 250 ppm of 2-chlorobutane vapouradded to the carrier gas stream. The CV spectrum shown in FIG. 8 bindicates that the presence of 250 ppm of 2-chlorobutane vapour in thenitrogen gas stream results in a decrease in the ability of the FAIMS toseparate the two main peaks that were observed in FIG. 8 a, and inaddition the CV of transmission has also become about 4 volts lessnegative. Each successive trace in the figure shows spectra obtained byincreasing the amount of 2-chlorobutane in 250 ppm increments up to 1000ppm. As shown in FIG. 8 c, at a level of 500 ppm of 2-chlorobutane inthe carrier gas, shoulders are observed on a broad peak suggestingseveral closely related species that are not well separated. Furtherincreases up to 1000 ppm, representing the maximum level that wasemployed in this study, continued to show improvements in the separationcapabilities in the CV spectra of m/z 1148.0 and shifts in the CV of iontransmission to more positive values. As shown in FIG. 8 e, at a levelof 1000 ppm of 2-chlorobutane there are 5 distinct peaks that appear inthe CV spectrum, each peak characterized by a mass-to-charge ratio of1148.0. This CV spectrum shows a dramatic change compared with the CVspectrum that was obtained without 2-chlorobutane present being presentin the carrier gas. Although a loss in signal intensity is observed,which is likely due to decreased ion focusing that is generallyassociated with lower magnitudes of CV, the addition of a trace amountof this “magic bullet” vapour has had the desired effect of enabling theseparation, in terms of CV, of species that were not separated in thepure nitrogen carrier gas using the same experimental conditions. Indirect contrast to previous reports, which have indicated that theseparation capabilities improve as the magnitude of the CV increases,improvements in separation capabilities have unexpectedly occurred witha decrease in the magnitude of CV. This observation, which is contraryto previously published knowledge, suggests that the improvements in theseparation capabilities are a result of a different mechanism than hasbeen described previously. As a result, the behavior shown in FIGS. 8 ato 8 e is not predicted nor expected based upon any previous knowledgeof FAIMS, including prior work which used mixed carrier gas.

The +6 charge state of bovine insulin was also experimentallyinvestigated in a similar manner, wherein the quadrupole mass analyzerwas set to selectively detect ions having an m/z value of 956.8 in orderto generate the CV spectra for this charge state. FIGS. 9 a to 9 e showfive CV spectra for the +6 charge state of bovine insulin using acarrier gas comprising purified nitrogen mixed with different amounts,for instance 0, 250, 500, 750, and 1000 ppm, respectively, of2-chlorobutane vapour. The ordinate in each plot represents the signalintensity of the +6 ion measured in counts per second and the abscissarepresents the CV range between +4 to −16 V. Referring to FIG. 9 b, forthe +6 charge state, there is a much more noticeable change in the CVspectrum, both in terms of the shape of the spectra and the CV values oftransmission, when only 250 ppm of 2-chlorobutane was added to thecarrier gas, as compared with the +5 charge state. The addition of only250 ppm of 2-chlorobutane resulted in a shift in the CV of transmissionof the most intense peak by about 6 volts more positive, with aconcomitant decrease in sensitivity of about 50%. Referring now to FIG.9 c, increasing the amount of 2-chlorobutane in the carrier gas to 500ppm resulted in additional unexpected improvements in separation. Unlikethe +5 charge state that showed significant improvements up to 1000 ppm,further increases in the amount of 2-chlorobutane in excess ofapproximately 500 ppm resulted only in modest improvements to theseparation capabilities of the +6 charge state while significantlydecreasing the observed signal intensity, as shown in FIGS. 9 d and 9 e.

It must be emphasized that these changes in the CV of transmission ofthe bovine insulin ions could not be predicted from any knowninformation about FAIMS, or known information about the ions of bovineinsulin. The mechanism giving rise to the changes of the CV spectrumshown in FIGS. 8 a to 8 e and in FIGS. 9 a to 9 e are currently not wellunderstood.

EXAMPLE 2

A fortuitous experimental observation led to the discovery that anunforeseen advantage can be obtained using water vapour as a specialtype of “magic bullet” vapour. This advantage corresponds to asignificant improvement in the observed signal intensities for somecompounds. Previous work has reported that high amounts of water vapourwill cause catastrophic deterioration of CV spectra. However, thepresence of water vapour at trace levels in the carrier gas stream hasnow been found to sometimes result in favorable changes to the CVspectra of some analytes. This unexpected behavior was observed whenanalyzing amphetamine and a series of related compounds. A gaspurification filter (charcoal/molecular sieves) that was used forremoving water vapour from a gas flow of nitrogen, which made up part ofthe carrier gas, was compromised by operation for a longer period oftime than the filter was designed to operate. Eventually as the sourcenitrogen gas passed through the filter, the filter was unable to removeall of the water in the source nitrogen gas. Although the carrier gasincluded a mixture of helium and nitrogen, as is described below, it wasonly the gas purification filter that was used with the source nitrogengas that was compromised so as to allow a small flow of water vapour,possibly at the sub-ppm level, to elute from the less than completelyeffective filter. Thus, some of the water vapour present in the sourcenitrogen gas was passed into the FAIMS device as part of the carriergas. Although the amount of water vapour was not quantified, the levelof water that was reported by the manufacturer in the source nitrogengas was approximately 3 ppm, which was subsequently diluted by theaddition of dehumidified helium.

Experimentally, the presence of water in the gas stream resulted in anincrease in the CV of transmission for the electrospray generated ionsof amphetamine and a series of related compounds, which moreimportantly, also lead to favorable changes in the signal intensity ofthe transmitted ions. A series of experiments were carried out onamphetamine, methamphetamine, and their methylenedioxy derivatives toillustrate the effects of water vapour on the CV spectra. Amphetamine(Am) and methamphetamine (Mam) were obtained from Alltech Associates(State College, Pa.). 3,4-Methylenedioxymethamphetamine (MDMAm),3,4-methylenedioxyamphetamine (MDAm), were obtained from CIL Inc.(Andover, Mass.). All of these compounds were obtained as solutions, ata concentration of 1 mg/mL in methanol. A composite stock solution, 10μg/mL of each of the four analytes, was prepared by combining aliquotsof each of the commercial standards and diluting with HPLC grademethanol (methanol). A “running solution”, containing approximately 50ppb of each of the four analytes, that was used for the analysis wasprepared by adding a known volume of the composite stock solution to aknown volume of solvent containing approximately 0.2 mM reagent gradeammonium acetate (0.2 mM ammonium acetate) in approximately 9:1methanol:distilled/deionized water (DDW) by volume. For example, forpreparing the running solution, 10 μL of the composite stock solutionand 1.99 mL were delivered to a glass vial using eppendorf pipets. Theglass vial was sealed with a screw top cap and shaken to ensurehomogeneity of the solution.

A 250 μL syringe was rinsed at least three times with a solution blank,such as for example a solution without the four analytes present andhaving approximately 0.2 mM ammonium acetate in approximately 9:1methanol:DDW by volume. The 250 μL syringe was rinsed at least threetimes with the running solution before filling the 250 μL syringe withthe running solution for analysis. The 250 μL syringe served as thesample reservoir 174 of FIG. 7, which was in fluid communication withthe electrospray needle 172 via the liquid delivery capillary 170 fortransferring the running solution from the 250 μL syringe to theelectrospray needle 172. The electrospray needle 172 was prepared usinga new piece of fused silica capillary of approximately 50 cm in lengthand having a 50 μm inner diameter and a 180 μm outer diameter, which wasfit into a 10-cm long stainless steel capillary having a 200 μm innerdiameter and 430 μm outer diameter, and allowed to protrude about 1 mmbeyond the end of the stainless steel. This stainless steel capillary,in turn, protruded about 5 mm beyond the end of a larger stainless steelcapillary of 15 cm in length with a 500 μm inner diameter and a 1.6 mmouter diameter, that was used for structural support and application ofthe high voltage necessary for electrospray. A Harvard® Apparatus Model22 syringe pump (not shown) was used to deliver the solution from the250 μL syringe to the end of the fused silica capillary at a flow rateof 1 μL/min. Prior to analyzing the running solution, the ionizationsource 72 was flushed with a solution blank at a flow rate of 1 μL/minfor 10 minutes.

The tip of the electrospray needle 172 was placed approximately 1 cmaway from, and slightly off-centre at an angle of approximately 45degrees to, the curtain plate electrode 156 of the domed-FAIMS device ofFIG. 7. Such an orientation of the electrospray needle 172 avoids thetransfer of large droplets into the FAIMS analyzer region 146. Theelectrospray needle 172 was held at approximately 3500 V generating acurrent of about 45 nA while spraying the running solution. To optimizethe electrospray process, the distance that the fused silica capillaryprotruded from the 10-cm long stainless steel capillary was adjusteduntil the current was stable at a value near 45 nA. The voltage on thecurtain plate electrode 156 was 1000 V and the curtain plate electrode156 was isolated from the FAIMS outer electrode 142. The outer electrode142 made electrical contact with the orifice plate of the massspectrometer, which were both held at +20 V. The FAIMS 70 was operatedin P2 mode; that is to say the asymmetric waveform has a negative DVvalue. The width of the FAIMS analyzer region 146 was approximately 2mm, and the width of an extraction region intermediate the curvedsurface terminus 148 of the inner electrode 140 and the ion outletorifice 152 was approximately 1.9 mm.

To generate the asymmetric waveform for the analyses described herein, atuned electronic circuit was used that provided an appropriatecombination of a sinusoidal wave and its harmonic. These waveforms weremathematically described by equation (1). The parameters of the waveformare the same as described above, with the exception of the CV, which wasscanned from +5 to −15 V.

The carrier gas comprised industrial grade nitrogen gas, which waspassed through a charcoal/molecular sieve filter, and industrial gradehelium gas, which was passed through a second charcoal/molecular sievefilter. Referring again to FIG. 2, these gases were mixed together inthe mixing chamber 66 with the flow rate of nitrogen into the mixingchamber 66 set to 1.4 L/min and the flow of helium set to 1.4 L/min.

For the spectra that were generated using the “dry filter”, thecharcoal/molecular sieve filter that was used with the nitrogen sourcegas had been recently regenerated by heating in an oven overnight whileflushing gas through to remove trapped water, and therefore this filterwas operating properly. For the spectra that are generated using “wetfilter”, the charcoal/molecular sieve filter that was used with thenitrogen source gas was compromised. For example, the filter had notbeen regenerated during two months of use and therefore the molecularsieves in these filters were only able to remove a portion, or none, ofthe water from the nitrogen source gas. The charcoal/molecular sievefilter that was used with the helium source gas was recently regeneratedand used for all the experiments.

The total gas flow splits into two portions including a first portionflowing out through the curtain plate orifice 154 in a direction that iscountercurrent to the arriving electrospray ions, thereby facilitatingdesolvation of the electrospray ions. A second portion of the total gasflow carries the ions inward through the ion inlet orifice 150 in theouter FAIMS electrode 142 and along the analyzer region 146 of thedevice.

Ions transmitted by the FAIMS device were detected using an API 300triple quadrupole mass spectrometer. Electrospray ionization of therunning solution produces ions for each of these four analytes of theform [M+H]⁺, where M is the molecular weight of the analyte and H is aproton. For analyzing electrospray generated ions of the four analytes,the m/z values of the [M+H]⁺ ion for each analyte was monitored as theCV was scanned. That is, when analyzing the running solution, the CV wasscanned from 5.0 to −15.0 V in 200 incremental steps of approximately−0.1 V each, while the following m/z values were monitored: 136.2 (Am),150.2 μm), 180.2 (MDAm), 194.2 (MDMAm). For example, when the CV scanwas initiated, the CV value was 5.0 V and the quadrupole mass analyzerbegan to selectively detect, one at a time, each of the four differentm/z values listed above during a time period of 100 ms each. After eachone of the four different m/z values was scanned, the CV was stepped to4.9 V and after a 100 ms pause time, each of the four different m/zvalues was selectively detected, one at a time, again. This process ofstepping the CV and selectively detecting each one of the four m/zvalues was repeated until a total of 201 points for each m/z value wasobtained. From this data, a plot of the ion intensity as a function ofthe CV was made for the [M+H]⁺ ion of each analyte. Two separate CVscans were carried out as described above, one with a “wet filter” andthe other with a “dry filter”. FIGS. 10 a through 13 a show the CV scansobtained for each analyte when a dry filter was used, and FIGS. 10 bthrough 13 b show the CV scans obtained for each analyte when a wetfilter was used.

FIGS. 10 a and 10 b show the CV spectrum that was acquired for MAm usinga dry filter and using a wet filter, respectively. As described above,the running solution containing the analyte was delivered by a flow ofsolution to an electrospray needle, continuously. The cloud of resultingions, including the [M+H]⁺ ion of MAm, was continuously delivered to theion inlet of FAIMS. FIG. 10 a shows a CV spectrum that was obtained whenthe gas purification filter was working properly, such that traces ofwater vapour were minimized in the carrier gas stream. For this analyte,the CV of optimal transmission was approximately +0.5 V and thecorresponding analyte intensity at this CV was approximately 140 000cps. When the “dry filter” was replaced with the “wet filter”, which wasunable to effectively remove the water present in the nitrogen gasstream, there was a shift in the optimal CV of transmission toapproximately −6.0 V, as shown in FIG. 10 b. Furthermore, the maximumintensity increased by approximately five-fold to 690 000 cps.

FIGS. 11 a and 11 b show the CV spectrum that was acquired for MDMAmusing a dry filter and using a wet filter, respectively. Clearly, MDMAmexhibits behavior similar to that of MAm under the conditions that wereused in the instant study. In particular, the presence of anapproximately same amount of water in the gas stream resulted in achange in the CV of transmission from approximately −1 to −6 V andapproximately a four-fold increase in the observed intensity from about210 000 cps to about 820 000 cps.

FIGS. 12 a and 12 b show the CV spectrum that was acquired for MDAmusing a dry filter and using a wet filter, respectively. The CV ofoptimal transmission for MDAm shows a shift from approximately 1.5 toapproximately −3.5 V, which is accompanied by an approximate 15-foldincrease in sensitivity when the “dry filter” is replaced with the “wetfilter”.

FIGS. 13 a and 13 b show the CV spectrum that was acquired for Am usinga dry filter and using a wet filter, respectively. The CV of optimaltransmission for Am shows a shift from approximately 4 to approximately−1.5 V with an approximately 15-fold increase in sensitivity when the“dry filter” is replaced with the “wet filter”.

In view of the CV spectra shown in FIGS. 10 through 13, it is apparentthat the degree of benefit of having trace amounts of water vapour inthe gas stream is dependent upon the type of ion being analyzed. For theinvestigation of the four ions shown in FIGS. 10 through 13, the mostnoticeable increase is observed for ions having positive or onlyslightly negative CV of optimal transmission, when operating using P2mode, in the absence of traces of water in the gas stream.Advantageously, introduction of a trace amount of water into the gasstream significantly lowers the detection limits of some types of ions.

The examples of the trace vapour used to describe this present inventionhave shown that the interaction between an analyte and the surroundinggas is very critical. Significant changes in the CV spectra are observedwhen very small quantities of vapour are added to the purified carriergas. The reason for this unexpected response is poorly understood. Someinteraction is assumed to take place between the ion and the added“magic bullet” vapour, however, the nature of the interaction and itseffect on ion transmission is currently unknown. This is not to say thatthe “magic bullet” vapours described herein will show improvements interms of signal intensity and/or peak separation for all analytes. Infact, compounds should be anticipated to respond differently to a given“magic bullet” vapour or even a mixture of “magic bullet” vapours. Inaddition, depending on the desired application, it might be possiblethat one “magic bullet” vapour could be used to improve the peakseparation capabilities, whereas a different “magic bullet” vapour couldbe used to improve the signal sensitivity.

Referring now to FIG. 14, shown a simplified flow diagram for a methodaccording to the instant invention of selectively transmitting ionswithin a FAIMS analyzer region using a carrier gas including a traceamount of an added component, a so called “magic bullet”, such as forinstance a dopant gas. At step 200, ions including an ion of interestare introduced into an analyzer region of a FAIMS. At step 202, a flowof a carrier gas is provided through the FAIMS analyzer region, thecarrier gas including at least a first gas and a trace amount of apredetermined dopant gas. The predetermined dopant gas is selected forimproving one of a peak separation and a signal intensity relating tothe ion of interest. At step 204, the ion of interest is selectivelytransmitted through the FAIMS analyzer region in the presence of thecarrier gas. Optionally, the method according to FIG. 14 includes a stepof varying the trace amount of the predetermined dopant gas to determinean optimal trace amount of the predetermined dopant gas for improvingone of the peak separation and the signal intensity relating to the ionof interest.

Referring now to FIG. 15, shown a simplified flow diagram for anothermethod according to the instant invention of selectively transmittingions within a FAIMS analyzer region using a carrier gas including atrace amount of an added component, such as for instance a dopant gas. AFAIMS analyzer region defined by a space between two spaced-apartelectrodes is provided at step 210. At step 212, an electric field isprovided within the FAIMS analyzer region resulting from the applicationof an asymmetric waveform voltage to at least one of the two electrodesand from the application of a direct-current compensation voltage to atleast one of the two electrodes. At step 214, a flow of a carrier gas isprovided from a carrier gas source. The flow of a carrier gas isprovided to a gas filter, such as for instance a charcoal/molecularsieve filter, to remove water and contaminants from the flow of acarrier gas at step 216, so as to obtain a flow of a purified carriergas. At step 218 a trace amount of a predetermined dopant gas is addedto the flow of a purified carrier gas to provide a flow of a dopedcarrier gas. At step 220, the flow of a doped carrier gas is introducedinto the FAIMS analyzer region. Ions including an ion of interest areintroduced into the FAIMS analyzer region at step 222, and at step 224the ion of interest is selectively transmitted through the FAIMSanalyzer region. Optionally, the method according to FIG. 15 includes astep of varying the trace amount of the predetermined dopant gas that isadded to the flow of a purified carrier gas, so as to determine anoptimal trace amount of the predetermined dopant gas.

Referring now to FIG. 16, shown a simplified flow diagram for yetanother method according to the instant invention of selectivelytransmitting ions within a FAIMS analyzer region using a carrier gasincluding a trace amount of an added component, such as for instance adopant gas. A FAIMS analyzer region defined by a space between twospaced-apart electrodes is provided at step 230. At step 232, anelectric field is provided within the FAIMS analyzer region resultingfrom the application of an asymmetric waveform voltage to at least oneof the two electrodes and from the application of a direct-currentcompensation voltage to at least one of the two electrodes. At step 234a suitable dopant gas is determined for improving at least one of a peakseparation and a signal intensity relating to an ion of interest. Atstep 236, a flow of a carrier gas is provided through the FAIMS analyzerregion, the carrier gas including a first gas and a trace amount of thesuitable dopant gas. At step 238, ions including the ion of interest areintroduced into the FAIMS analyzer region. At step 240, the ions ofinterest are selectively transmitted through the analyzer region.

The term dopant gas includes vapours produced by substances that arenormally a liquid or a solid at standard temperature and pressure, aswell as substances that are normally in the gaseous state at standardtemperature and pressure. Optionally, the dopant gas is provided to themixing chamber as an undiluted flow of the dopant gas, in particular asource of the dopant gas does not comprise another gas mixed with thedopant gas.

Numerous other embodiments may be envisaged without departing from thespirit and scope of the invention.

1. An apparatus for selectively transmitting ions comprising: a highfield asymmetric waveform ion mobility spectrometer comprising twoelectrodes defining an analyzer region therebetween, the two electrodesdisposed in a spaced apart arrangement for allowing ions to propagatetherebetween and for providing an electric field within the analyzerregion resulting from the application of an asymmetric waveform voltageto at least one of the two electrodes and from the application of acompensation voltage to at least one of the two electrodes, forselectively transmitting an ion of interest at a given combination ofasymmetric waveform voltage and compensation voltage; and, a dopingportion for receiving a flow of a carrier gas from a gas source and forcontrollably mixing a dopant gas with the flow of a carrier gas toproduce a doped carrier gas stream containing a predeterminedconcentration of the dopant gas, the doping portion also in fluidcommunication with the analyzer region for providing the doped carriergas stream thereto, wherein during use the doped carrier gas stream thatis provided to the analyzer region contains less than 1% dopant gas byvolume.
 2. An apparatus according to claim 1, comprising a source of adopant gas in fluid communication with the doping portion.
 3. Anapparatus according to claim 2, wherein the source of a dopant gascomprises a containing portion for containing a first gas mixtureincluding up to approximately 1% dopant gas by volume.
 4. An apparatusaccording to claim 2, wherein the source of a dopant gas comprises acontaining portion for containing a first gas mixture including up toapproximately 2500 ppm dopant gas.
 5. An apparatus according to claim 1,wherein the doping portion is in fluid communication with a second gassource for providing a second separate flow of a carrier gas that,during use, is controllably mixed with the doped carrier gas flow priorto the doped carrier gas flow being introduced into the analyzer region,to provide a diluted doped carrier gas flow for introduction into theanalyzer region.
 6. An apparatus for selectively transmitting ionscomprising: a high field asymmetric waveform ion mobility spectrometercomprising two electrodes defining an analyzer region therebetween, thetwo electrodes disposed in a spaced apart arrangement for allowing ionsto propagate therebetween and for providing an electric field within theanalyzer region resulting from the application of an asymmetric waveformvoltage to at least one of the two electrodes and from the applicationof a compensation voltage to at least one of the two electrodes, forselectively transmitting an ion of interest at a given combination ofasymmetric waveform voltage and compensation voltage; a carrier gassource for providing a flow of a carrier gas; a first containing portionfor containing a first gas mixture including a first concentration of adopant gas; a second containing portion for containing a second gasmixture including a second concentration of the dopant gas; and, adoping portion in fluid communication with the carrier gas source, thefirst containing portion, the second containing portion and the analyzerregion, for receiving the flow of a carrier gas from the gas source andfor controllably mixing at least one of the first gas mixture and thesecond gas mixture with the flow of the carrier gas, to form a dopedcarrier gas stream containing a predetermined concentration of thedopant gas, and for providing the doped carrier gas stream to theanalyzer region, wherein during use the doped carrier gas stream that isprovided to the analyzer region contains less than 1% dopant gas byvolume.
 7. An apparatus according to claim 6, wherein, during use, thefirst containing portion contains a first gas mixture including up toapproximately 1% dopant gas by volume.
 8. An apparatus according toclaim 6, wherein, during use, the second containing portion contains asecond gas mixture including between 0% dopant gas by volume and 1%dopant gas by volume.
 9. An apparatus according to claim 6, wherein thedoping portion comprises a flow selector for selectively mixing one orthe other of the first gas mixture and the second gas mixture with theflow of a carrier gas.
 10. An apparatus according to claim 6, whereinthe doping portion comprises a flow combiner for mixing a controlledamount of the first gas mixture and a controlled amount of the secondgas mixture with the flow of a carrier gas.
 11. A method of selectivelytransmitting ions, comprising the steps of: introducing ions includingan ion of interest into an analyzer region of a high field asymmetricwaveform ion mobility spectrometer; providing a flow of a doped carriergas other than air through the analyzer region, the doped carrier gasincluding a carrier gas and a trace amount of a predetermined dopantgas, the predetermined dopant gas selected for improving at least one ofa peak separation and a signal intensity relating to the ion of interestrelative to the peak separation and the signal intensity relating to theion of interest in the presence of the carrier gas only; and,selectively transmitting the ion of interest through the analyzer regionin the presence of the doped carrier gas.
 12. A method according toclaim 11, wherein the predetermined dopant gas is water vapour.
 13. Amethod according to claim 11, wherein the predetermined dopant gas is avapour produced from an inorganic compound other than water.
 14. Amethod according to claim 11, wherein the predetermined dopant gas is avapour produced from an organic compound.
 15. A method according toclaim 14, wherein the organic compound is a halogenated compound.
 16. Amethod according to claim 11, wherein the flow of a doped carrier gascomprises between 1 ppm and 10,000 ppm of the predetermined dopant gas.17. A method according to claim 16 wherein the flow of a doped carriergas comprises between 25 ppm and 1,000 ppm of the predetermined dopantgas.
 18. A method according to claim 11, comprising the step ofproviding a flow of a second doped carrier gas through the analyzerregion, the second doped carrier gas including a carrier gas and a traceamount of a second predetermined dopant gas, the second predetermineddopant gas selected for improving the other one of the at least one of apeak separation and a signal intensity relating to the ion of interestrelative to the peak separation and the signal intensity relating to theion of interest in the presence of the carrier gas only.
 19. A methodaccording to claim 11, comprising the step of varying the trace amountof the predetermined dopant gas to determine an optimal trace amount ofthe predetermined dopant gas for improving the at least one of a peakseparation and a signal intensity relating to the ion of interest.
 20. Amethod of selectively transmitting ions, comprising the steps of:providing an analyzer region defined by a space between two spaced-apartelectrodes; providing an electric field within the analyzer regionresulting from the application of an asymmetric waveform voltage to atleast one of the two electrodes and from the application of adirect-current compensation voltage to at least one of the twoelectrodes; providing a flow of a carrier gas from a carrier gas source;removing water vapour from the flow of a carrier gas to provide a flowof a dried carrier gas; adding a trace amount of a predetermined dopantgas to the flow of a dried carrier gas to provide a flow of a dopedcarrier gas; introducing the flow of a doped carrier gas into theanalyzer region; introducing ions including an ion of interest into theanalyzer region; and, selectively transmitting the ion of interestthrough the analyzer region in the presence of the doped carrier gas.21. A method according to claim 20, comprising the steps of: varying theapplied compensation voltage to selectively transmit the ions ofinterest through the analyzer region in the presence of the flow of adried carrier gas so as to obtain a first compensation voltage spectrum;obtaining a plurality of other compensation voltage spectra, eachcompensation voltage spectrum of the plurality of other compensationvoltage spectra obtained by varying the applied compensation voltage toselectively transmit the ions of interest through the analyzer region inthe presence of one of a plurality of a different dopant gases; and,selecting as the predetermined dopant gas one of the dopant gases of theplurality of different dopant gases on the basis of a difference betweenthe compensation voltage spectrum obtained using the one of the dopantgases and the first compensation voltage spectrum.
 22. A methodaccording to claim 20, wherein the predetermined dopant gas is watervapour.
 23. A method according to claim 20, wherein the predetermineddopant gas is a vapour produced from an inorganic compound other thanwater.
 24. A method according to claim 20, wherein the predetermineddopant gas is a vapour produced from an organic compound.
 25. A methodaccording to claim 24, wherein the organic compound is a halogenatedspecies.
 26. A method according to claim 20, wherein the flow of a dopedcarrier gas comprises between 1 ppm and 10,000 ppm of the predetermineddopant gas.
 27. A method according to claim 20, wherein the flow of adoped carrier gas comprises between 25 ppm and 1,000 ppm of thepredetermined dopant gas.
 28. A method according to claim 20, comprisingthe step of varying the trace amount of the predetermined dopant gas todetermine an optimal trace amount of the predetermined dopant gas in theflow of a doped carrier gas.
 29. A method of selectively transmittingions, comprising the steps of: providing an analyzer region defined by aspace between two spaced-apart electrodes; providing an electric fieldwithin the analyzer region resulting from the application of anasymmetric waveform voltage to at least one of the two electrodes andfrom the application of a direct-current compensation voltage to atleast one of the two electrodes; determining a suitable dopant gas forimproving one of a peak separation and a signal intensity relating to anion of interest; providing a flow of a carrier gas other than airthrough the analyzer region, the carrier gas including a first gas and atrace amount of the suitable dopant gas; introducing ions including theion of interest into the analyzer region; and, selectively transmittingthe ion of interest through the analyzer region.
 30. A method accordingto claim 29, wherein the step of determining a suitable dopant gasincludes a step of determining an optimal amount of the suitable dopantgas for improving the one of a peak separation and a signal intensityrelating to the ion of interest.
 31. A method according to claim 29,comprising the step of determining a suitable second dopant gas forimproving the other one of a peak separation and a signal intensityrelating to the ion of interest.
 32. A method according to claim 31,wherein the step of determining a suitable second dopant gas includes astep of determining an optimal amount of the suitable second dopant gasfor improving the other one of a peak separation and a signal intensityrelating to the ion of interest.
 33. A method according to claim 31,wherein one of the suitable dopant gas and the suitable second dopantgas is water vapour.
 34. A method according to claim 31, wherein atleast one of the suitable dopant gas and the suitable second dopant gasis a vapour produced from an inorganic compound other than water.
 35. Amethod according to claim 31, wherein at least one of the suitabledopant gas and the suitable second dopant gas is a vapour produced froman organic compound.
 36. A method according to claim 35, wherein theorganic compound is a halogenated species.
 37. A method according toclaim 29, wherein the flow of a carrier gas comprises between 1 ppm and10,000 ppm of the suitable dopant gas.
 38. A method according to claim29, wherein the flow of a doped carrier gas comprises between 25 ppm and1,000 ppm of the suitable dopant gas.